The long-term objective of the proposed research is the further characterization of the intrinsic cardiac nerves (ICN) and their role in the regulation of cardiac function. The experiments will employ both a four-chamber isovolumic in situ heart preparation and an in vitro isolated atrial model. Using both electrical and pharmacological means of stimulating the ICN, we will attempt to answer the following biological questions: 1) Is ICN activity modulated by cardiac afferent nerves, either with or without the participation of the CNS? 2) Do the ventricles actually possess ICN cell bodies or are their responses to nicotinic stimulation mediated by postganglionic parasympathetic axons whose cell bodies lie in the atria? 3) What are the relative contributions of pre-junctional and post-junctional changes to the ICN supersensitivity which follows extrinsic surgical denervation of the heart? 4) Are responses of the ICN to nicotine mediated primarily by receptors on the axons or cell bodies? 5) What is the dysrhythmogenic potential of nicotine and how do the adrenergic and ICN components of its action contribute to it? Understanding the functional capabilities of the ICN and its mode of regulation will add to our general understanding of how this neural apparatus fits into the overall schema of neural control of the heart. In addition, this study will help to clarify the manner in which the ICN may influence the response of the transplanted heart to physiological and pharmacologic stimuli.